SKNA as a biomarker for cardiovascular events

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PROJECT SUMMARY The objective of this application is to test the hypothesis that skin sympathetic nerve activity (SKNA) can be used as a biomarker for physiological events including predicting neurological recovery during therapeutic hypothermia for cardiac arrest, and to risk stratify patients for recurrence of atrial fibrillation (AF) following catheter ablation. The concept that sympathetic nerve activity (SNA) could be determined from recordings obtained from the skin originated from studies that have shown that sympathetic tone is important in cardiac arrhythmogenesis. The research labs at the Krannert Institute of Cardiology have successfully developed methods to record autonomic nerve activity in ambulatory canine models from either subcutaneous tissues or on the surface of the skin (SKNA). We found that both subcutaneous nerve activity and SKNA closely correlated with stellate ganglia nerve activity in ambulatory canine models. SKNA recordings were then validated and translated to human patients and it was recently documented that sympathetic nerve activity correlates to the onset of atrial and ventricular arrhythmias. In this proposal, we will now apply SKNA recordings to be used as a biomarker for neurological status in patients that are undergoing targeted temperature management (TTM) for cardiac arrest and to risk stratify patients for AF recurrence after undergoing ablation therapy. There are more than 350,000 out-of-hospital cardiac arrests taking place every year and they are associated with poor survival rates, with 31% for shockable rhythms and 11% for all rhythms combined. Anoxic brain injury accounts for a significant majority of morbidity and mortality in post-cardiac arrest patients. In this context, TTM is one of the only interventions that has been shown to be neuroprotective and improve neurologic outcomes after cardiac arrest. Despite this, cerebral ischemia may persist for several hours and an accurate short-term assessment of neurological outcome in patients undergoing TTM remains a challenge. Significantly low SKNA or an altered SKNA relationship with heart rate during TTM could signify autonomic dysregulation. Atrial fibrillation (AF) is a progressive disease that commonly advances into persistent and then permanent AF. The longer AF continues, the outcome of any associated therapeutic options becomes less favorable. Percutaneous catheter ablation is commonly used as a therapy for AF, however recurrence of AF after ablation remains an issue. With SKNA recordings, we can now visualize and analyze the nerve activity that can trigger AF, and risk stratify patients for AF recurrence post ablation. The purpose of this project is to use SKNA recordings as a biomarker for (1) neurologic outcome in patients undergoing TTM post-cardiac arrest; (2) to risk stratify patients for AF recurrence after catheter ablation. This present research grant application is designed to test the hypothesis that SKNA is a useful biomarker and a potential surrogate end point for future clinical investigations in common cardiovascular diseases, and to provide new insights into the neural mechanisms of diseases.